This application proposes to examine brain function associated with response to cognitive therapy (CT) for recurrent unipolar depression. Depression is a common, debilitating disorder and treatment of severe depression is often difficult. Rumination or involuntary elaboration on negative topics is a salient symptom linked to depressive severity and duration. Evidence from cognitive and affective neuroscience suggests that such sustained emotional information processing could result from decreased inhibition of brain areas that automatically process emotional information by brain areas responsible for executive control such as the prefrontal cortex. Initial data suggests that depressed individuals suffer from increased amygdala and decreased prefrontal activity, and that CT is likely to target these mechanisms. Yet, these links have not been tested directly. This proposal requests funds to examine whether increased and sustained limbic and ventromedial prefrontal activity during emotional information processing tasks and decreased dorso-lateral prefrontal cortex activity during cognitive tasks are associated with recovery from unipolar depression in CT. Recovery in CT is expected to be strongest for individuals who display pre-treatment disruptions in these functions, which are targeted by CT. Thus, CT is further expected to decrease limbic reactivity and improve executive control. 60 depressed individuals will be assessed using functional magnetic resonance imaging during tasks requiring cognitive and emotional information processing before and after 12-14 weeks of CT; 21 healthy individuals will also be scanned twice to understand expected changes in brain activity overtime that are unrelated to recovery. Positive results could help to understand which individuals are likely to recover in CT, the mechanisms by which this efficacious intervention leads to recovery in depressed individuals, how cognitive and physiological aspects of depression are related to recovery, and validation for the proposed mechanisms of action for CT. Negative results would suggest that CT may depend on different mechanisms of action than have been proposed by the cognitive neuroscience community. This project will be executed in conjunction with an ongoing clinical trial through which the intervention will be provided.